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Cited by 63Cellular Mechanics and InteractionsDevelopmental Biology and Gene RegulationAxon Guidance and Neuronal Signaling

PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells

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McDonald, Jocelyn A., Khodyakova, Anna, Aranjuez, George, Dudley, Colleen, Montell, Denise J.·2008·Current Biology
DOI 10.1016/j.cub.2008.09.041PMC PMC2593744
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Abstract

Background Many cells that migrate during normal embryonic development or in metastatic cancer first detach from an epithelium. However, this step is often difficult to observe directly in vivo, and the mechanisms controlling the ability of cells to leave the epithelium are poorly understood. In addition, once cells detach, they must assume a migratory phenotype, involving changes in cytoskeletal and signaling dynamics. Drosophila border cells provide a model system in which a combination of forward genetics and live-cell imaging can allow researchers to investigate the cellular and molecular mechanisms of epithelial cell detachment and migration in vivo. Results We identified the Drosophila homolog of the serine/threonine kinase PAR-1 (MARK/Kin1) in a screen for mutations that disrupt border cell migration. Previous studies identified two proteins, Apontic and Notch, that indirectly affect border cell detachment by regulating transcription of downstream targets. In contrast, PAR-1 directly modulates apical-basal polarity between border cells and epithelial cells to promote detachment. Furthermore, PAR-1, but not the apical polarity complex protein PAR-3, promotes the directionality of transient cell protrusions, which border cells require for sensing the chemoattractant gradient. Conclusions We conclude that PAR-1-dependent apical-basal polarity is required for proper detachment of migratory border cells from neighboring epithelial cells. Moreover, polarity controlled by PAR-1 influences the ability of migratory cells to sense direction, a critical feature of migration. Thus, this work reveals new insights into two distinct, but essential, steps of epithelial cell migration.

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Research works printed but not linked: 35

  1. [1]Jang AC Starz-Gaiano M Montell DJ Modeling migration and metastasis in Drosophila J. Mammary Gland Biol. Neoplasia 2007 12 103 114 17549611
  2. [2]Prasad M Montell DJ Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging Dev. Cell 2007 12 997 1005 17543870
  3. [3]Starz-Gaiano M Melani M Wang X Meinhardt H Montell DJ Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population Dev. Cell 2008 14 726 738 18477455
  4. [4]Wang X Adam JC Montell D Spatially localized Kuzbanian required for specific activation of Notch during border cell migration Dev. Biol 2007 301 532 540 17010965
  5. [5]Bai J Uehara Y Montell DJ Regulation of invasive cell behavior by Taiman, a Drosophila Protein Related to AIB1, a steroid receptor coactivator amplified in breast cancer Cell 2000 103 1047 1058 11163181
  6. [6]Liu Y Montell DJ Identification of mutations that cause cell migration defects in mosaic clones Development 1999 126 1869 1878 10101121
  7. [7]Silver DL Montell DJ Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila Cell 2001 107 831 841 11779460
  8. [8]Mathieu J Sung HH Pugieux C Soetaert J Rorth P A sensitized PiggyBac-based screen for regulators of border cell migration in Drosophila Genetics 2007 176 1579 1590 17483425 PMC1931525
  9. [9]Goldstein B Macara IG The PAR proteins: fundamental players in animal cell polarization Dev. Cell 2007 13 609 622 17981131 PMC2964935
  10. [10]Benton R St Johnston D Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells Cell 2003 115 691 704 14675534
  11. [11]Cox DN Lu B Sun TQ Williams LT Jan YN Drosophila par-1 is required for oocyte differentiation and microtubule organization Curr. Biol 2001 11 75 87 11231123
  12. [12]Doerflinger H Benton R Shulman JM St Johnston D The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium Development 2003 130 3965 3975 12874119
  13. [13]Drewes G Ebneth A Preuss U Mandelkow EM Mandelkow E MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption Cell 1997 89 297 308 9108484
  14. [15]Sun TQ Lu B Feng JJ Reinhard C Jan YN Fantl WJ Williams LT PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling Nat. Cell Biol 2001 3 628 636 11433294
  15. [16]Sapir T Sapoznik S Levy T Finkelshtein D Shmueli A Timm T Mandelkow EM Reiner O Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration J. Neurosci 2008 28 5710 5720 18509032 PMC6670809
  16. [17]Borghese L Fletcher G Mathieu J Atzberger A Eades WC Cagan RL Rorth P Systematic analysis of the transcriptional switch inducing migration of border cells Dev. Cell 2006 10 497 508 16580994 PMC2955450
  17. [18]Wang X Bo J Bridges T Dugan KD Pan TC Chodosh LA Montell DJ Analysis of cell migration using whole-genome expression profiling of migratory cells in the Drosophila ovary Dev. Cell 2006 10 483 495 16580993
  18. [19]Shulman JM Benton R St Johnston D The Drosophila homolog of C. elegans PAR-1 organizes the oocyte cytoskeleton and directs oskar mRNA localization to the posterior pole Cell 2000 101 377 388 10830165
  19. [20]Niewiadomska P Godt D Tepass U DE-Cadherin Is required for intercellular motility during Drosophila Oogenesis J. Cell Biol 1999 144 533 547 9971747 PMC2132905
  20. [21]Pinheiro EM Montell DJ Requirement for Par-6 and Bazooka in Drosophila border cell migration Development 2004 131 5243 5251 15456726
  21. [22]Hurd TW Fan S Liu CJ Kweon HK Hakansson K Margolis B Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia Curr. Biol 2003 13 2082 2090 14653998
  22. [23]Brajenovic M Joberty G Kuster B Bouwmeester T Drewes G Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network J. Biol. Chem 2004 279 12804 12811 14676191
  23. [25]Spicer J Rayter S Young N Elliott R Ashworth A Smith D Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1 Oncogene 2003 22 4752 4756 12879020
  24. [26]Martin SG St Johnston D A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity Nature 2003 421 379 384 12540903
  25. [28]Hurov JB Watkins JL Piwnica-Worms H Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity Curr. Biol 2004 14 736 741 15084291
  26. [29]Suzuki A Hirata M Kamimura K Maniwa R Yamanaka T Mizuno K Kishikawa M Hirose H Amano Y Izumi N aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity Curr. Biol 2004 14 1425 1435 15324659
  27. [30]Vaccari T Rabouille C Ephrussi A The Drosophila PAR-1 spacer domain is required for lateral membrane association and for polarization of follicular epithelial cells Curr. Biol 2005 15 255 261 15694310
  28. [31]Fulga TA Rorth P Invasive cell migration is initiated by guided growth of long cellular extensions Nat. Cell Biol 2002 4 715 719 12198500
  29. [32]Somogyi K Rorth P Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration Dev. Cell 2004 7 85 93 15239956
  30. [33]Montell DJ Rørth P Spradling AC slow border cells, a locus required for a developmentally regulated cell migration during oogenesis, encodes Drosophila C/EBP Cell 1992 71 51 62 1394432
  31. [34]Chen X Macara IG Par-3 controls tight junction assembly through the Rac exchange factor Tiam1 Nat. Cell Biol 2005 7 262 269 15723052
  32. [35]Hirose T Izumi Y Nagashima Y Tamai-Nagai Y Kurihara H Sakai T Suzuki Y Yamanaka T Suzuki A Mizuno K Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation J. Cell Sci 2002 115 2485 2495 12045219
  33. [36]Ozdamar B Bose R Barrios-Rodiles M Wang HR Zhang Y Wrana JL Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity Science 2005 307 1603 1609 15761148
  34. [37]Aranda V Haire T Nolan ME Calarco JP Rosenberg AZ Fawcett JP Pawson T Muthuswamy SK Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control Nat. Cell Biol 2006 8 1235 1245 17060907
  35. [38]Lee M Vasioukhin V Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor J. Cell Sci 2008 121 1141 1150 18388309

Cited by

Sorted by citations

Authors
McDonald, J. A., Khodyakova, A., Aranjuez, G., Dudley, C., & Montell, D. J.
Affiliations
  • Cleveland Clinic (US)
  • Johns Hopkins University (US)
Corresponding author
  • McDonald, Jocelyn A.
  • Montell, Denise J.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2008-11
Volume
18
Issue
21
Pages
1659-1667
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2008.09.041
PMC
PMC2593744
OpenAlex
W1984562849
Cited by
63
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 6
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (R01GM073164, R01GM078526, R01GM46425)
  • Cleveland Clinic
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
MARK kinases, border cell migration, epithelial cell detachment, apical-basal polarity, Par3, Drosophila, epithelial-mesenchymal transition, cell polarity
MeSH terms
AMP-Activated Protein Kinase Kinases, Animals, Cell Adhesion, Cell Movement, Drosophila, Epithelial Cells, Protein Kinases, Cell Polarity, Protein Serine-Threonine Kinases, Cell Surface Extensions, Drosophila Proteins, Glycogen Synthase Kinase 3

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